Toxoplasma gondii infection and its implications within the central nervous system

• Published in: Nature reviews. Microbiology 2021-07, Vol.19 (7), p.467-480
• Main Authors: Matta, Sumit K., Rinkenberger, Nicholas, Dunay, Ildiko R., Sibley, L. David
• Format: Article
• Language: English
• Subjects: 631/250/2499; 631/326/417; 631/326/421; 631/326/88; Animals; Biomedical and Life Sciences; Care and treatment; Central nervous system; Central nervous system diseases; Central Nervous System Infections - immunology; Central Nervous System Infections - parasitology; Central Nervous System Infections - pathology; Chronic Disease; Cysts; Development and progression; Disease control; Host-parasite relationships; Humans; Immune clearance; Immune privilege; Immune response; Infections; Infectious Diseases; Inflammation; Interferon; Interferons - immunology; Life Sciences; Medical Microbiology; Microbiology; Mortality; Muscles; Nervous system; Observations; Opportunist infection; Parasites; Parasitology; Review Article; Signs and symptoms; Survival; Toxoplasma - growth & development; Toxoplasma - pathogenicity; Toxoplasma - physiology; Toxoplasma gondii; Toxoplasmosis; Toxoplasmosis - drug therapy; Toxoplasmosis - immunology; Toxoplasmosis - parasitology; Virology; Virulence; Virulence factors
• ISSN: 1740-1526; 1740-1534
• DOI: 10.1038/s41579-021-00518-7

Toxoplasma gondii is a parasite that infects a wide range of animals and causes zoonotic infections in humans. Although it normally only results in mild illness in healthy individuals, toxoplasmosis is a common opportunistic infection with high mortality in individuals who are immunocompromised, most commonly due to reactivation of infection in the central nervous system. In the acute phase of infection, interferon-dependent immune responses control rapid parasite expansion and mitigate acute disease symptoms. However, after dissemination the parasite differentiates into semi-dormant cysts that form within muscle cells and neurons, where they persist for life in the infected host. Control of infection in the central nervous system, a compartment of immune privilege, relies on modified immune responses that aim to balance infection control while limiting potential damage due to inflammation. In response to the activation of interferon-mediated pathways, the parasite deploys an array of effector proteins to escape immune clearance and ensure latent survival. Although these pathways are best studied in the laboratory mouse, emerging evidence points to unique mechanisms of control in human toxoplasmosis. In this Review, we explore some of these recent findings that extend our understanding for proliferation, establishment and control of toxoplasmosis in humans. Toxoplasmosis caused by the parasite Toxoplasma gondii is a common opportunistic infection with high mortality in individuals who are immunocompromised, most commonly due to reactivation of infection in the central nervous system (CNS). In this Review, Sibley and colleagues explore the interaction between host immune defences and parasite virulence factors with emphasis on bradyzoite differentiation and survival of T. gondii within the CNS.